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Posted: June 23, 2010

Biomaterials for nanomedicine: Smooth delivery

(Nanowerk News) Porous silica can form stable and biocompatible nanometer-sized hollow spheres, or vesicles, that are suitable for transporting and delivering drugs to their targets in the body. The clinical use of silica vesicles, however, has been obstructed by the tendency for the spheres to clump into aggregates in water-based solutions. A team led by Ye Liu from the A*STAR Institute of Materials Research and Engineering in Singapore has now circumvented this problem by attaching water-soluble, brush-shaped polymers called polyethylene glycol (PEG) to the shells of the silica vesicles ("Poly(ethylene glycol)-Graft-Hollow Silica Vesicles for Drug Delivery").

The researchers prepared nanometer-sized silica spheres from a precursor known as TEOS using polystyrene beads as templates. Then, after removing the templates by heating, they modified the outer surface of the spheres with nitrogen-containing organic linkers that reacted easily with the PEG polymers to produce polymer-functionalized vesicles.

In addition to dispersing well in solution, the newly synthesized vesicles maintained their small size even in highly diluted aqueous solutions. They also remained intact for over a year, highlighting their long shelf-life and stability.

The team evaluated the performance of the vesicles for the delivery of paclitaxel (PTX), a potent but highly toxic water-insoluble anti-tumor drug (Fig. 1). According to Liu, formulations that are currently available for PTX delivery improve the water-solubility of the drug but can induce other side effects.

Liu and his team filled the pores and cavity of the vesicles with the drug by immersing the spheres in a saturated PTX solution in methanol. They found that the nanometer-sized vesicles released PTX more efficiently than the free drug in buffer solution, which forms micrometer-sized particles.

"As we understand it, the mechanism of the release of encapsulated PTX and free PTX is similar," says Liu. "However, the PTX contained in the silica vesicles is nano-sized so its release rate is higher."

The researchers also incubated the PTX-filled vesicles in human breast- and brain-cancer cells and demonstrated that the encapsulated drug was more potent than free PTX in vitro. By labeling the vesicles with a green fluorescent dye, they discovered that the drug delivery system readily penetrated the malignant cells, explaining the potency of encapsulated PTX in killing cancer cells.

The team is currently planning to test the PEG polymer-functionalized silica vesicles for the delivery of PTX in vivo. "These vesicles could be taken as a platform for encapsulation and delivery of various species such as other drugs and fragrances," says Liu. "We are developing other types of polymer-functionalized hollow silica vesicles to produce stable smart systems for the encapsulation and delivery of pharmaceuticals and cosmetics."